R&D and Price Elasticity of Demand

This note explores the relationship between the price elasticity of demand and the R&D intensity of the product. We introduce the concept of R&D intensity into a standard Dixit-Stiglitz/Krugman-type setting. R&D activity is treated as a fixed cost of production. Within this framework, sectors with a higher R&D intensity show a lower price elasticity of demand. This proposition is confirmed by an empirical investigation of export demand for manufactured goods from major industrialised countries. Consequently, real exchange rate changes have an impact on the commodity structure of exports.R&D intensity; Price elasticity; Exports

Interim Results of a Multicenter Trial with the New Electronic Subretinal Implant Alpha AMS in 15 Patients Blind from Inherited Retinal Degenerations

Purpose: We assessed the safety and efficacy of a technically advanced subretinal electronic implant, RETINA IMPLANT Alpha AMS, in end stage retinal degeneration in an interim analysis of two ongoing prospective clinical trials. The purpose of this article is to describe the interim functional results (efficacy). Methods: The subretinal visual prosthesis RETINA IMPLANT Alpha AMS (Retina Implant AG, Reutlingen, Germany) was implanted in 15 blind patients with hereditary retinal degenerations at four study sites with a follow-up period of 12 months (www.clinicaltrials.gov NCT01024803 and NCT02720640). Functional outcome measures included (1) screen-based standardized 2- or 4-alternative forced-choice (AFC) tests of light perception, light localization, grating detection (basic grating acuity (BaGA) test), and Landolt C-rings; (2) gray level discrimination; (3) performance during activities of daily living (ADL-table tasks). Results: Implant-mediated light perception was observed in 13/15 patients. During the observation period implant mediated localization of visual targets was possible in 13/15 patients. Correct grating detection was achieved for spatial frequencies of 0.1 cpd (cycles per degree) in 4/15; 0.33 cpd in 3/15; 0.66 cpd in 2/15; 1.0 cpd in 2/15 and 3.3 cpd in 1/15 patients. In two patients visual acuity (VA) assessed with Landolt C- rings was 20/546 and 20/1111. Of 6 possible gray levels on average 4.6 ± 0.8 (mean ± SD, n = 10) were discerned. Improvements (power ON vs. OFF) of ADL table tasks were measured in 13/15 patients. Overall, results were stable during the observation period. Serious adverse events (SAEs) were reported in 4 patients: 2 movements of the implant, readjusted in a second surgery; 4 conjunctival erosion/dehiscence, successfully treated; 1 pain event around the coil, successfully treated; 1 partial reduction of silicone oil tamponade leading to distorted vision (silicon oil successfully refilled). The majority of adverse events (AEs) were transient and mostly of mild to moderate intensity. Conclusions: Psychophysical and subjective data show that RETINA IMPLANT Alpha AMS is reliable, well tolerated and can restore limited visual functions in blind patients with degenerations of the outer retina. Compared with the previous implant Alpha IMS, longevity of the new implant Alpha AMS has been considerably improved. Alpha AMS has meanwhile been certified as a commercially available medical device, reimbursed in Germany by the public health system

Heart failure after pressure overload in autosomal-dominant desminopathies: Lessons from heterozygous DES-p.R349P knock-in mice

Background Mutations in the human desmin gene (DES) cause autosomal-dominant and -recessive cardiomyopathies, leading to heart failure, arrhythmias, and AV blocks. We analyzed the effects of vascular pressure overload in a patient-mimicking p.R349P desmin knock-in mouse model that harbors the orthologue of the frequent human DES missense mutation p. R350P. Methods and results Transverse aortic constriction (TAC) was performed on heterozygous (HET) DES-p.R349P mice and wild-type (WT) littermates. Echocardiography demonstrated reduced left ventricular ejection fraction in HET-TAC (WT-sham: 69.5 ± 2.9%, HET-sham: 64.5 ± 4.7%, WTTAC: 63.5 ± 4.9%, HET-TAC: 55.7 ± 5.4%; p<0.01). Cardiac output was significantly reduced in HET-TAC (WT sham: 13088 ± 2385 μl/min, HET sham: 10391 ± 1349μl/min, WT-TAC: 8097 ± 1903μl/min, HET-TAC: 5793 ± 2517μl/min; p<0.01). Incidence and duration of AV blocks as well as the probability to induce ventricular tachycardias was highest in HET-TAC. We observed reduced mtDNA copy numbers in HET-TAC (WT-sham: 12546 ± 406, HET-sham: 13526 ± 781, WT-TAC: 11155 ± 3315, HET-TAC: 8649 ± 1582; p = 0.025), but no mtDNA deletions. The activity of respiratory chain complexes I and IV showed the greatest reductions in HET-TAC. Conclusion Pressure overload in HET mice aggravated the clinical phenotype of cardiomyopathy and resulted in mitochondrial dysfunction. Preventive avoidance of pressure overload/arterial hypertension in desminopathy patients might represent a crucial therapeutic measure

Desmin Knock-Out Cardiomyopathy: A Heart on the Verge of Metabolic Crisis

Desmin mutations cause familial and sporadic cardiomyopathies. In addition to perturbing the contractile apparatus, both desmin deficiency and mutated desmin negatively impact mitochondria. Impaired myocardial metabolism secondary to mitochondrial defects could conceivably exacerbate cardiac contractile dysfunction. We performed metabolic myocardial phenotyping in left ventricular cardiac muscle tissue in desmin knock-out mice. Our analyses revealed decreased mitochondrial number, ultrastructural mitochondrial defects, and impaired mitochondria-related metabolic pathways including fatty acid transport, activation, and catabolism. Glucose transporter 1 and hexokinase-1 expression and hexokinase activity were increased. While mitochondrial creatine kinase expression was reduced, fetal creatine kinase expression was increased. Proteomic analysis revealed reduced expression of proteins involved in electron transport mainly of complexes I and II, oxidative phosphorylation, citrate cycle, beta-oxidation including auxiliary pathways, amino acid catabolism, and redox reactions and oxidative stress. Thus, desmin deficiency elicits a secondary cardiac mitochondriopathy with severely impaired oxidative phosphorylation and fatty and amino acid metabolism. Increased glucose utilization and fetal creatine kinase upregulation likely portray attempts to maintain myocardial energy supply. It may be prudent to avoid medications worsening mitochondrial function and other metabolic stressors. Therapeutic interventions for mitochondriopathies might also improve the metabolic condition in desmin deficient hearts

Die embryonale Resorption – eine ultrasonographische Längsschnittstudie an der Modellart Europäischer Feldhase (Lepus europaeus PALLAS, 1778)

Embryonic resorption is a common phenomenon in polytocous mammals. The process of resorption is not associated with any obvious clinical symptoms. Therefore, studies are usually based on post mortem examinations or counts after ovariohysterectomy (OHE). The present study is the first longitudinal in vivo investigation describing the incidence and morphology of embryos undergoing resorption in a small polytocous species, the European brown hare (Ebh) (Lepus europaeus). High frequency ultrasonographic examinations enabled early detection of resorption sites from day 8 of pregnancy onwards. Resorptions were monitored in context of embryonic and fetal development and classified into (i) preimplantation resorptions, (ii) peri-implatation resorptions and (iii) post-implantation resorptions. In total, 42% of embryos underwent resorption. Parallel monitoring of the ovaries revealed in 91% of the cases the regression of a CL while an embryo underwent resorption. The number of resorptions did not significantly differ from the number of CL in regression suggesting a one-resorption-to-one-regression-relationship. Two minimally invasive ultrasound guided biopsy techniques were established for the genetic analysis of resorption sites. Resorption material was gained in vivo by aspiration of resorption fluid or by biopsy of extraembryonic tissue from the placenta (CVS). Further analysis was performed by microsatellite analysis (paternity testing) and SRY testing. Paternity was determined in 11 of the fluid aspirates (n = 28) and six of the placental biopsies (n = 8). The lower success rate in the fluid samples is attributed to the high abundance of maternal cells which was confirmed by analysis of fluid sample smears. By SRY testing male sex of the resorbing embryo was identified in ten of the fluid samples (n =28) and one of the placental samples (n = 8). A negative influence of the biopsy techniques on the viability of the remaining embryos or the reproductive performance of the mother was not observed.Die embryonale Resorption ist ein Phänomen, das bei allen polytoken Säugetiere auftritt. Da der Resorptionsprozess nicht mit deutlich erkennbaren klinischen Symptomen assoziiert ist, beruhen Studien in der Regel auf post mortem Zählungen oder Zählungen nach Ovariohysterektomie (OHE). Die vorliegende Studie beschäftigt sich mit der Resorptionsrate und Morphologie embryonaler Resorptionen beim Europäischen Feldhasen (EFh) (Lepus europaeus). Zum ersten Mal wurden bei einem kleinen polytoken Säugetier in vivo Langzeituntersuchungen von embryonalen Resorptionen durchgeführt. Hochauflösende Ultraschalluntersuchungen ermöglichten die Detektion embryonaler Resorptionen ab Tag 8 der Trächtigkeit. Dabei wurden die Resorptionen im Zusammenhang mit der embryonalen und fetalen Entwicklung ultrasonographisch untersucht und in (i) prä-implantative, (ii) periimplantative und (iii) post-implantative Resorptionsstadien eingeteilt. Insgesamt wurden 42% aller Embryonen resorbiert. Parallele Verlaufsuntersuchungen der Ovarien zeigten, dass in 91% der Fälle der Resorptionsprozess von einem regressierenden GK begleitet wurde. Dabei unterschied sich die Anzahl an Resorptionen nicht signifikant von der Anzahl regressierender GK, was auf einen Eins-zu-eins-Zusammenhang zwischen Resorption und GK-Regression hinweisen könnte. Die Entwicklung von zwei ultraschall-gestützten Biopsietechniken ermöglichte weitergehende genetische Untersuchungen des in Resorption befindlichen Embryos. Resorptionsmaterial wurde in vivo gewonnen durch Aspiration von Resorptionsflüssigkeit oder durch Stanzbiopsie von extraembryonalem Plazentagewebe. Anschließend wurde das Material mittels Mikrosatelliten-Analyse (Vaterschaftsnachweis) und SRY-Gen- Bestimmung analysiert. Bei 11 der Aspirationsbiopsien (n = 28) und sechs der Plazentabiopsien (n = 8) konnte die Vaterschaft bestimmt werden. Die geringere Erfolgsrate bei den Aspirationsbiopsien lässt sich auf eine hohe Abundanz mütterlicher Zellen in der Aspirationsflüssigkeit zurückführen, was durch Analyse des Aspirationsbioptats in Ausstrichen bestätigt werden konnte. Die Identifizierung des männlichen Geschlechts durch SRY-Gen-Bestimmung gelang bei 10 der Aspirationsbiopsien (n = 28) und einer der Plazentabiopsien (n = 8). Ein negativer Einfluss der Biopsietechniken auf die weitere Entwicklung der verbleibenden Embryonen oder die zukünftige Fortpflanzungsleistung der Mutter konnte nicht beobachtet werden

A Note on R&D and Price Elasticity of Demand

This note explores the relationship between the price elasticity of demand and the R&D intensity of the product. We introduce the concept of R&D intensity into a standard Dixit-Stiglitz/Krugmann-type setting. R&D activity is treated as a ficed cost of production. Within this framework, sectors with a higher R&D intensity show a lower price elasticity of demand. This proposition is confirmed by an empirical investigation of export demand for manufactured goods from major industrialised countries. Consequently, real exchange rate changes have an impact on the commodity structure of exports.R&D intensity, price elasticity, exports